DESCRIPTION: The overall goal of this application is to establish the mechanisms controlling the activity of Dbl-related guanine nucleotide exchange factors, a highly conserved family of GEFs specific for Rho GTPases. The investigator will utilize biochemical and genetic approaches to attain the following five specific aims: 1) To determine whether Src-related kinases can phosphorylate and modulate GEF activity of Dbl-related molecules. 2) To examine the functional role of PH domains of Dbl-related GEFs. 3) To investigate the significance of the interaction of Vav, a Dbl-related GEF, with components of the Ras signal transduction pathways. 4) To examine the structural basis underlying the specificity of recognition of Rho GTPases by Dbl-related GEFs. 5) To identify residues in Dbl-related GEFs which are critical for interaction with Rho GTPases.